This application seeks renewed CCSG funding for the City of Hope Comprehensive Cancer Center (COHCCC). The COHCCC brings together 131 Members from 34 Departments in the City of Hope Medical Center and the Beckman Research Institute. The Center receives $24,212,096M (Totals) from NCI, $25,947,483M from other peer-reviewed sources, and $31,421,929M from non-peer-reviewed sources, for a total of $81,581,508M in overall funding. Through faculty recruitment, reorganization, and significant infrastructure development, the COHCCC has greatly enhanced its ability to accelerate clinical and translational cancer-focused research. Seventy-two new faculty have been recruited, including 48 clinical investigators and 24 basic and population research scientists. The Cancer Center has five Programs: Molecular Oncology (MONC), Developmental Cancer Therapeutics (DCT), Cancer Immunotherapeutics (CI), Hematologic Malignancies (HM), and Cancer Control and Population Sciences (CCPS). Center membership has been honed to sharpen cancer focus and an Associate Member category has been created for investigators whose potential for peer-reviewed, cancer-focused research is yet developing. This application requests support for ten Shared Resources: Analytical Cytometry, Analytical Pharmacology, Bioinformatics, Functional Genomics/Genomic Sequencing, Pathology, Small Animal Imaging, Drug Discovery and Structural Biology, Survey Research, Biostatistics, and Clinical Protocol and Data Management. The COHCCC is primed to make significant advances in the coming years. Our 72 new basic, population and clinical research recruits will continue to introduce new ideas, technologies, and areas of research focus while enhancing the creative and innovative environment of the Center. Significant infrastructure and other resources have been created to facilitate the translation of discoveries to the rapid development of new cancer treatments, diagnostic tests, and other interventions that would aid people with cancer, as well as individuals at risk for malignancy. Finally, the overall configuration of the institution and its administrative capabilities in terms of leadership, programmatic alignment, development, and authority that have been augmented so that the Cancer Center will be more responsive to its members and to harness their collective energies and creativity. This proposal documents that the COHCCC has built a solid structure for achieving its missions and is stronger and more sustainable than it has ever been.